Ikaros confers early temporal competence to mouse retinal progenitor cells.
In the developing mouse retina, multipotent retinal progenitor cells (RPCs) give rise to specific retinal cell types at different times, but the molecular mechanisms regulating how RPCs change over time remain unclear. In the Drosophila neuroblast lineage, the zinc finger transcription factor Hunchback (Hb) is both necessary and sufficient to specify early-born neuronal identity. We show here that Ikaros, a mouse ortholog of Hb, is expressed in all early embryonic RPCs, which then give rise to Ikaros-negative RPCs at later stages in the lineage. Remarkably, misexpression of Ikaros in late RPCs is sufficient to confer competence to generate early-born neurons. Conversely, Ikaros mutant mice have reduced numbers of early-born cell types, whereas late-born cell types are not affected. These results suggest a model in which Ikaros expression is both necessary and sufficient to confer early temporal competence to RPCs and raise the possibility that a similar strategy might be used to control the sequential order of cell birth in other parts of the nervous system.
Elliott
Jimmy
J
Institut de recherches cliniques de Montréal (IRCM), Cellular Neurobiology Research Unit, Montréal, QC H2W 1R7, Canada.
Jolicoeur
Christine
C
Ramamurthy
Vasanth
V
Cayouette
Michel
M
D000818:Animals; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor